Inhibitory effect of 6-hydroxy-7-methoxychroman-2-carboxylic acid phenylamide on nitric oxide and interleukin-6 production in macrophages

Life Sci. 2005 Nov 4;77(25):3242-57. doi: 10.1016/j.lfs.2005.05.046. Epub 2005 Jun 22.

Abstract

6-Hydroxy-7-methoxychroman-2-carboxylic acid phenylamide (CP compound) is a novel chemically synthetic compound with vitamin E-like chemical structure. In the present study, the CP compound was discovered to inhibit nitric oxide (NO) and interleukin (IL)-6 productions in lipopolysaccharide (LPS)-stimulated macrophages. Further, CP compound attenuated LPS-induced synthesis of mRNA and protein levels of inducible NO synthase (iNOS), in parallel, and inhibited iNOS promoter activity. In the similar way, CP compound inhibited LPS-induced synthesis of IL-6 transcript but also IL-6 promoter activity. These results indicate that CP compound could down-regulate LPS-induced iNOS and IL-6 expression at the transcription step. As a mechanism of the anti-inflammatory action shown by CP compound, suppression of LPS-induced activation of both nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) has been documented. Finally, CP compound could provide an invaluable tool to investigate LPS-induced NF-kappaB and AP-1 activation, in addition to its therapeutic potential in NO- and IL-6-associated inflammatory diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Chromans / pharmacology*
  • Down-Regulation
  • Interleukin-6 / biosynthesis*
  • Lipopolysaccharides / pharmacology
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / enzymology
  • Macrophages, Peritoneal / metabolism
  • Male
  • Mice
  • Mice, Inbred ICR
  • NF-kappa B / metabolism
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase / biosynthesis
  • Nitric Oxide Synthase Type II
  • Transcription Factor AP-1 / metabolism

Substances

  • 6-hydroxy-7-methoxychroman-2-carboxylic acid phenylamide
  • Chromans
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Transcription Factor AP-1
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse